The artificial sweetener 4,1',6'-trichloro-4,1',6'-trideoxyoalactosucrose ("sucralose") is derived from sucrose by replacing the hydroxyls in the 4, 1', and 6' positions with chlorine. (In the process of making the sweetener, the stereo configuration at the 4 position is reversed - hence the compound is a qalactosucrose.) The direction of the chlorine atoms to only the desired positions is a major synthesis problem because the hydroxyls that are replaced are of differing reactivity; two are primary and one is secondary. The synthesis is further complicated by the fact that the primary hydroxyl in the 6 position is unsubstituted in the final product.
A number of different synthesis routes for the preparation of sucralose have been developed in which the reactive hydroxyl in the 6 position is first blocked, as by an ester group, prior to the chlorination of the hydroxyls in the 4, 1', and 6' positions, followed by hydrolysis to remove the ester substituent to produce sucralose. Several of such synthesis routes involve tin-mediated syntheses of sucrose-6-esters. Illustrative are the tin-mediated routes disclosed by Navia (U.S. Pat. No. 4,950,746), Neiditch et al. (U.S. Pat. No. 5,023,329), Wingard et al. (U.S. patent application Ser. No. 870,190, filed Apr. 13, 1992--published, as EP-A-0 475 619 A1), and Walkup et al. (U.S. Pat. No. 5,089,608 - Walkup et al.-I).
The above-illustrated tin-mediated syntheses have in common the preparation of a sucrose-6-ester that can be chlorinated to produce a sucralose-6-ester (that is, sucralose having an ester group substituent at the 6 position). The sucrose-6-ester can be chlorinated by the process described in Walkup et al., U.S. Pat. No. 4,980,463 (Walkup et al.-II). The Walkup et al.-II process produces as a product of the chlorination a mixture of 6-O-acyl-4,1',6'-trichloro-4,1',6'-trideoxyoalactosucrose ("sucralose-6-ester") in a tertiary amide solvent such as N,N-dimethylformamide. The chlorination reaction product mixture also contains water, salts, and chlorinated carbohydrate byproducts.
The present invention provides an improved method for producing sucralose from a mixture of 6-O-acyl-4,1',6'-trichloro-4,1',6'-trideoxyoalactosucrose in a tertiary amide solvent such as N,N-(dimethylformamide.